o c T s The pathologic diagnosis of lung cancer is undergoing a remarkable transformation, largely driven by new therapies that are dependent on histologic type and/or molecular changes.1 Lung cancer is diagnosed pathologically by a histologic or cytologic approach. Because 70% of lung cancer patients present in advanced stages, the diagnosis is established by small biopsies or cytologies. However, previous classifications by the World Health Organization (WHO) have not specifically addressed this problem. Because of the rapid advances in lung adenocarcinoma occurring at every level, there is a new lung adenocarcinoma classification sponsored by the International Association for the Study of Lung Cancer, American Thoracic Society, and the European Respiratory Society (IASLC/ATS/ERS) and developed by an international multidisciplinary panel, including pathologists, molecular biologists, oncologists, radiologists, and thoracic surgeons.1 This new classification will result in significant changes in the 2004 WHO Classification (Table 1). For the first time in the history of lung cancer, new terminology are proposed for classification of lung cancer in small biopsies and cytology (Table 2). This review will focus primarily on the histologic features of lung cancer by addressing the new classification both in resected specimens as well as small biopsies and cytology. In the past, because of different therapeutic approaches, the major differential diagnostic issue in lung cancer for pathologists has been the distinction of small cell lung carcinoma (SCLC) versus nonsmall cell lung carcinoma (NSCLC). However, in the past 6 years, 3 new therapeutic advances have defined the importance of classifying NSCLC further to distinguish squamous cell carcinoma from adenocarcinoma or other histologic types. A major advance was the discovery that EGFR mutations are almost always found in adenocarcinomas and that in advanced lung adenocarcinoma patients they predict a better outcome and response to tyrosine kinase inhibitors (TKIs) as first-line therapy, whereas those without EGFR mutations have a better outcome with chemotherapy.2–5 In addition because of the risk of life-threatening